Stroma cell-derived factor-1Î± (SDF-1Î±) is a cardioprotective chemokine, acting through its G-protein coupled receptor CXCR4. In experimental acute myocardial infarction, administration of SDF-1Î± induces an early improvement of systolic function which is difficult to explain solely by an anti-apoptotic and angiogenic effect. We wondered whether SDF-1Î± signaling might have direct effects on calcium transients and beating frequency. Primary rat neonatal cardiomyocytes were culture-expanded and characterized by immunofluorescence staining. Calcium sparks were studied by fluorescence microscopy after calcium loading with the Fluo-4 acetoxymethyl ester sensor. The cardiomyocyte enriched cellular suspension expressed troponin I and CXCR4 but was vimentin negative. Addition of SDF-1Î± in the medium increased cytoplasmic calcium release. The calcium response was completely abolished by using a neutralizing anti-CXCR4 antibody and partially suppressed and delayed by preincubation with an inositol triphosphate receptor (IP3R) blocker, but not with a ryanodine receptor (RyR) antagonist. Calcium fluxes induced by caffeine, a RyR agonist, were decreased by an IP3R blocker. Treatment with forskolin or SDF-1Î± increased cardiomyocyte beating frequency and their effects were additive. In vivo, treatment with SDF-1Î± increased left ventricular dP/dtmax. These results suggest that in rat neonatal cardiomyocytes, the SDF-1Î±/CXCR4 signaling increases calcium transients in an IP3-gated fashion leading to a positive chronotropic and inotropic effect.

Aims The two-pore-domain potassium channel TASK-1 is robustly inhibited by the activation of receptors coupled to the GÎ±q subgroup of G-proteins, but the signal transduction pathway is still unclear. We have studied the mechanisms by which endothelin receptors inhibit the current carried by...

Beta-arrestins (Î²-arrestin1 and Î²-arrestin2) are known as cytosolic proteins that mediate desensitization and internalization of activated G protein-coupled receptors. In addition to these functions, Î²-arrestins have been found to work as adaptor proteins for intracellular signaling...

Functionally selective signaling appears to contribute to the variability in mechanisms that underlie tolerance to the antinociceptive effects of opioids. The present study tested this hypothesis by examining the contribution of G protein-coupled receptor kinase (GRK)/Protein kinase C (PKC) and...

Aims Investigation of Gq signalling with pharmacological agonists of Gq-coupled receptors lacks spatio-temporal precision. The aim of this study was to establish melanopsin, a light-sensitive Gq-coupled receptor, as a new tool for the investigation of spatial and temporal effects of Gq...

G-protein-coupled receptors (GPCRs) are the most abundant receptors in the heart and therefore are common targets for cardiovascular therapeutics. The activated GPCRs transduce their signals via heterotrimeric G-proteins. The four major families of G-proteins identified so far are specified...